Tumor suppressor protein p53 promotes 2-methoxyestradiol-induced activation of Bak and Bax, leading to mitochondria-dependent apoptosis in human colon cancer HCT116 cells.

Tumor suppressor protein p53 promotes 2-methoxyestradiol-induced activation of Bak and Bax, leading to mitochondria-dependent apoptosis in human colon cancer HCT116 cells. J Microbiol Biotechnol. 2014 Sep 1; Authors: Lee JY, Lee SB, Park WY, Choi YJ, Kim B, Kim YH, Jun DY, Kim YH Abstract To examine the effect of tumor suppressor protein p53 on the antitumor activity of 2-methoxyestradiol (2-MeO-E2), 2-MeO-E2-induced cell cycle changes and apoptotic events were compared between human colon carcinoma cell lines HCT116 (p53+/+) and HCT116 (p53-/-). When both cell types were exposed to 2-MeO-E2, a reduction in the cell viability and an enhancement in the proportions of G2/M cells and apoptotic sub-G1 cells commonly occurred dose-dependently. These 2-MeO-E2-induced cellular changes, except for G2/M arrest, appeared to be more apparent in the presence of p53. Immunofluorescence microscopic analysis using anti--tubulin and anti-lamin B2 antibodies revealed that after 2-MeO-E2 treatment, impaired mitotic spindle network and prometaphase arrest occurred similarly in both cell types. Following 2-MeO-E2 treatment, only HCT116 (p53+/+) cells exhibited an enhancement in the levels of p53, p-p53 (Ser-15), p21WAF1/CIP1, and Bax; however, the Bak level remained relatively constant in both cell types, and the Bcl-2 level decreased only in HCT116 (p53+/+) cells. Additionally, mitochondrial apoptotic events, including activation of Bak and Bax, los...
Source: Journal of Microbiology and Biotechnology - Category: Biotechnology Authors: Tags: J Microbiol Biotechnol Source Type: research